This 2-year R03 application has, as its specific objectives, the quantitative assessment of oral bioavailability of the putative cancer chemopreventive compounds present in green tea. These water-soluble, aromatic polyphenolic compounds are referred to as catechins. The activity of those compounds has been established from numerous in vitro and in vivo animal studies. Human clinical trials sponsored by the NCI are currently being conducted. The activity of those compounds has been established from numerous in vitro and in vivo animal studies. Human clinical trials sponsored by the NCI are currently being conducted. The compounds that have been identified include (i)-epigallocatechin-3- gallate (EGCG). Interest has focused on EGCG, since it appears to have the greatest activity. A critical , but sometimes overlooked issue in in vivo studies, is the completeness of oral absorption (bioavailability). Studies conducted to date have fatal flaws in experimental design. Therefore, we know little about the disposition and bioavailability of those compounds. We propose to develop a porcine model to characterize the disposition and bioavailability of EGCG following intravenous (iv) and oral dosing of two capsule formulations that are currently being used in clinical trials: "pure" and "polyphenol-E". The former contains the pure chemical form of EGCG and the latter is a more crude mixture of EGCG and the other cathechins. The porcine model (Yucatan minipig) is proposed because of the similarity of the gastrointestinal physiology and anatomy with humans. Furthermore, the swine appears to metabolize drugs in a fashion similar to humans. In year 01 each of 6 animals will receive a single iv dose (50-100 mg) and a single 200 mg dose of EGCG in the form of a "pure" and "polyphenol-E" capsule. Depending upon the estimation of within- and between-animal variation, a more powerful design may be employed, the semi-simultaneous, single, extended single occasion design. These data will provide a complete characterization of the disposition and the absolute and relative bioavailability of EGCG. In Year 02 the effect of dose will be evaluated in a5-way cross-over study where each of 6 animals will be given an iv will permit calculation of absolute and relative bioavailability of EGCG and relative bioavailability of the other cathechins. A significant point that needs to be stressed, is that we will evaluate the same oral capsules in the porcine model that are being used in human clinical trials. This will permit a direct comparison of results from the porcine model with those from humans. The long-term aims of this proposal are to employ the porcine model to characterize the disposition kinetics and bioavailability of cancer chemopreventive and anti-cancer agents.